Engineered heart slices for electrophysiological and contractile studies

Abstract

A major consideration in the design of engineered cardiac tissues for the faithful representation of physiological behavior is the recapitulation of the complex topography and biochemistry of native tissue. In this study we present engineered heart slices (EHS), which consist of neonatal rat ventricular cells (NRVCs) seeded onto thin slices of decellularized cardiac tissue that retain important aspects of native extracellular matrix (ECM). To form EHS, rat or pig ventricular tissue was sectioned into 300 μm-thick, 5 to 16 mm-diameter disks, which were subsequently decellularized using detergents, spread on coverslips, and seeded with NRVCs. The organized fiber structure of the ECM remained after decellularization and promoted cell elongation and alignment, resulting in an anisotropic, functional tissue that could be electrically paced. Contraction decreased at higher pacing rates, and optical mapping revealed electrical conduction that was anisotropic with a ratio of approximately 2.0, rate-dependent shortening of the action potential and slowing of conduction, and slowing of conduction by the sodium channel blocker lidocaine. Reentrant arrhythmias could also be pace-induced and terminated. EHS constitute an attractive in vitro cardiac tissue in which cardiac cells are cultured on thin slices of decellularized cardiac ECM that provide important biochemical, structural, and mechanical cues absent in traditional cell cultures.